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Untreated Myelodysplastic SyndromePhase 1/2NCT05782127

Oral Azacitidine Combined With Venetoclax in Previously Untreated Higher-risk Myelodysplastic Syndromes

A Phase 1/2 study testing Onureg + Venetoclax in people with Untreated Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 25 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase I/II open-label, dose-finding, multi-center study will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Untreated Myelodysplastic Syndrome
What is being tested?
Onureg + Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
25 sitesFrance
Study dates
6 Dec 2023to Nov 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must understand and voluntarily sign and date an ICF indicating the investigational nature of the study, approved by an independent EC/IRB, prior to the initiation of any screening or study-specific procedures.
  • Age ≥ 18 years at the date of signing the ICF.
  • Diagnosis of MDS according to the 2016 WHO classification (13) (Appendix 1), with presence of < 20% bone marrow blasts per bone marrow aspirate at screening, confirmed by local investigator with HR-MDS, based on the revised International Prognostic Scoring System (IPSS-R) >3 (intermediate, high or very high) (14) (Appendix 2) and a blast percentage of 5 or more.
  • Previously untreated HR-MDS: no prior therapy for MDS with any hypomethylating agents (azacitidine or decitabine), chemotherapy, allo-Hematopoietic Stem Cell Transplantation (HSCT) or experimental agent. All other treatments are not considered prior therapy.
  • Not immediately eligible for allo-HSCT or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
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  • Total white blood cell (WBC) count ≤ 10 G/L; Treatment with hydroxyurea is permitted to lower the WBC to reach this inclusion criterion and will be stopped at least 48 hours before treatment initiation.
  • Adequate liver functions as demonstrated by:
  • Serum alanine transaminase (ALT) < 3.0 × upper limit of normal [ULN];
  • Serum aspartate transaminase (AST) < 3.0 × ULN;
  • Serum total bilirubin ≤ 2.0 × ULN (except in the setting of isolated Gilbert syndrome, where participants may only be included with total bilirubin ≤ 3.0 x ULN)
  • Adequate renal function with calculated creatinine clearance ≥ 40 mL/min/1.73 m² (estimation based on Modification of Diet in Renal Disease (MDRD) formula or CKD-EPI, by local laboratory).
  • Participant is able to communicate with the investigator, and has the ability to comply with the requirements of the study procedures, available for regular blood sampling, study related assessments, including bone marrow aspirates and appropriate clinical management at the treating institution for the duration of the study.
  • Females of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). FCBP must agree to undergo medically supervised pregnancy test prior to starting study drug, during the course of the study, and after end of study therapy:
  • Have one negative pregnancy test as verified by the Investigator prior to starting study therapy. The first pregnancy test will be performed at screening (within 3 days prior to first study drug administration), and a negative urinary test before starting all subsequent cycles. This applies even if the participant practices true abstinence from heterosexual contact or agree to use, and be able to comply with highly effective contraception without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 6 months after last dose of Onureg, or at least 1 month after the last dose of venetoclax, whichever is later or longer if required by local regulations.
  • Female patients are either post-menopausal, free from menses for > 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agree to abstain from becoming pregnant throughout the study, starting with Visit 1. Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study and for 6 months (females and males) following the last dose of treatment.
  • Male participants must practice true abstinence (which must be reviewed on a monthly basis) or agree to use an adequate method of contraception for the duration of the study. Men should be advised not to father a child while receiving treatment and for 3 months post study. Men must agree to learn about the procedures for preservation of sperm before starting treatment.

Who cannot join

  • Previous treatment for MDS, any approved or investigational antineoplastic agents or radiotherapy.
  • Previous diagnosis of:
  • MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
  • MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
  • Participant has an active, uncontrolled systemic fungal, bacterial, or viral infection. The participant should be afebrile and off antibiotics for at least 72 hours and off antifungals for 7 days. In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved and based on Investigator assessment in consultation with the Medical Monitor, there are no sequelae that would place the patient at a higher risk of receiving investigational treatment.
  • History of clinically significant medical conditions, laboratory abnormality, psychiatric illness or any other reason that the investigator determines would interfere with the subject's participation in this study, would make the subject an unsuitable candidate to receive study drug or predisposes the participant to high risk of noncompliance with the protocol.
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  • History of active malignancy within the past year prior to screening, with the exception of:
  • Adequately treated carcinoma in situ of the uterine cervix
  • Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
  • Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy.
  • Patients with ongoing horomonotherapy could be included.
  • Participant has received strong or moderate CYP3A inhibitors or inducers or p-gp inhibitors within 7 days prior to initiation of study treatment with prolonged treatment required without therapeutic alternatives. Azols are the only exception and may be permitted after cycle 1 at investigator's discretion and will result in venetoclax dose reduction.
  • Consumption of grapefruit products, Seville oranges or starfruit within 3 days prior to first dose of venetoclax.
  • Received live attenuated vaccines prior to initiation of study treatment.
  • History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.
  • Conditions that could interfere with drug absorption including short gut syndrome, dysphagia, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
  • Participant has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg) or has not been stable for at least 1 month prior to treatment.
  • Significant active cardiac disease within the previous 6 months prior to signing the ICF, including:
  • New York Heart Association (NYHA) Class III or IV congestive heart failure
  • Unstable angina or angina requiring surgical or medical intervention
  • Significant cardiac arrhythmia
  • And/or myocardial infarction
  • Participant is a pregnant or lactating female.
  • Participant has known or suspected to have hypersensitivity to any of the components of the assigned study treatments.
  • Positive test result(s) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Subjects with serologic evidence of prior vaccination to hepatitis B virus (i.e., hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B surface [HBs] antibody positive and anti-hepatitis B core [HBc] antibody negative) may participate.
  • Absence of social security affiliation.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

France25 sites

  • CHU d'Amiens Picardie - Site sud

    Amiens, 80054

  • CHU d'Angers

    Angers, 49033

  • Hôpital Avicenne

    Bobigny, 93009

  • Hôpital privé Sévigné

    Cesson-Sévigné, 35510

  • CH Annecy Genevois

    Épagny, 74370

  • CHU de Grenoble

    Grenoble, 38043

  • CH Le Mans

    Le Mans, 72037

  • Hôpital Saint Vincent de Paul

    Lille, 59020

  • CHU de Limoges - Hôpital Dupuytren

    Limoges, 87042

  • CH Lyon sud

    Lyon, 69495

  • Institut Paoli Calmettes

    Marseille, 13009

  • CHI Mont-de-Marsan

    Mont-de-Marsan, 40000

  • CHU Saint Eloi

    Montpellier, 34295

  • CHU Hôtel Dieu

    Nantes, 44093

  • Hôpital Archet 1

    Nice, 06200

  • CHU Nîmes - Institut de Cancérologie du Gard

    Nîmes, 30029 cedex 9

  • Hôpital Saint Louis

    Paris, 75010

  • Hôpital Cochin

    Paris, 75014

  • CHU de Haut-Lévèque

    Pessac, 33604

  • CHU de Poitiers

    Poitiers, 86021

  • Centre Henri Becquerel

    Rouen, 76038

  • IUCT Oncopole

    Toulouse, 31059

  • CHU de Tours - Hôpital Bretonneau

    Tours, 37000

  • CH Valence

    Valence, 26000

  • Hôpital Brabois

    Vandœuvre-lès-Nancy, 54500

Other trials in France

About this study

Official title: A Phase I/II, Open-label, Single Arm, Multicenter Dose-finding Study Assess the Safety and Preliminary Efficacy of Oral Azacitidine CC-486 (ONUREG) in Combination With Venetoclax (VENCLYXTO) in Previously Untreated Higher-risk Myelodysplastic Syndromes Ineligible for Allogenic Transplantation

This phase I/II open-label, dose-finding, multi-center study will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with higher-risk myelodysplastic syndromes (HR-MDS) not eligible to transplant.

Read the detailed description

During phase I, three dose features of Onureg will be tested in combination with a fixed dose of Venetoclax to define the optimal biological dose for phase II.

The phase II will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with HR-MDS not eligible to transplant.

Being tested
Onureg + Venetoclax
Keywords
MDS, Oral Azacitidine, Venetoclax

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Onureg + VenetoclaxDrug

    Also called CC-486 + ABT-199

    Combination of Onureg and Venetoclax

Study groups in NCT05782127
Study groupRoleWhat they receive
Onureg + VenetoclaxExperimentalOnureg (CC-486, oral azacitidine) will be administered orally at 200 or 300 mg once daily for 7 or 14 consecutive days, beginning on Day 1 of repeated 28-day cycles. Venetoclax will be administered orally at 400 mg once daily for 14 consecutive days on days 1 to 14, beginning on Day 1 of repeated 28-day cycles. Patients will be treated up to 4 cycles and for a maximum of 24 cycles.
Receives: Drug: Onureg + Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity

    Dose-limiting toxicities according to CTCAE (common terminology criteria for adverses events) 5.0 occurring within the first cycle of treatment

    Measured: at day 28 of cycle 1

  2. Overall response

    Overall response measured after the first cycle of treatment according to modified IWG-MDS (International Working Group-Myelodysplastic Syndromes) 2006

    Measured: at day 28 of cycle 1

Secondary outcomes (15)

  1. Best response

    Best response evaluated according to the modified IWG-MDS 2006 and IWG-HR-MDS 2023 criteria

    Measured: after 6 cycles of treatment (each cycle is 28 days)

  2. Hematological improvement

    Hematological improvement (erythroid, neutrophil and platelet improvement) according to IWG-MDS 2006 and IWG-HR-MDS 2023

    Measured: at end of treatment (an average of 4 years)

  3. Time to response

    Time from onset of treatment to date of achievement of any response according to the modified IWG-MDS 2006 criteria

    Measured: at end of treatment (an average of 4 years)

  4. Duration of response

    Time interval between the first date of achievement of any response according to the modified IWG-MDS 2006 criteria to relapse

    Measured: at end of study (an average of 5 years)

  5. Progression to acute myeloid leukemia (AML)

    Rate of transformation to AML

    Measured: at end of treatment (an average of 4 years)

  6. Time to next treatment

    Time from onset of trial treatment to onset of subsequent therapy

    Measured: at end of study (an average of 5 years)

  7. Survival

    Determination of overall survival rate, event-free survival rate, progression-free survival rate

    Measured: at end of study (an average of 5 years)

  8. Transfusion independence

    Rate of red blood cells and platelets transfusion independance for transfusion-dependent patients at baseline

    Measured: at end of study (an average of 5 years)

  9. Duration of transfusion independence

    Time interval between the achievement of transfusion independence and relapse with need of transfusion

    Measured: at end of study (an average of 5 years)

  10. Identification and grading of adverse events

    Toxicity profile of study treatment including identification and grading of adverse events based on NCI CTCAE version 5, cytopenia duration, life-threatening or fatal cytopenias rate, unscheduled hospitalization rate, infectious complications rate, red blood cells and platelets transfusions needs

    Measured: at end of treatment (an average of 4 years)

  11. Patient-reported outcomes according to FACIT-AN

    Patient-reported outcomes according to Functional Assessment of Chronic Illness Therapy - anemia (FACIT-An) version 4 (Score range: 0-188), evaluation of of change in QoL from baseline

    Measured: at end of treatment (an average of 4 years)

  12. Early mortality

    Determination of early mortality rate at day 28

    Measured: at day 28

  13. Patient-reported outcomes according to EQ-5D-5L

    Patient-reported outcomes according to 5-level EuroQol-5D (EQ-5D-5L) (Scale numbered from 0 to 100), evaluation of change in QoL from baseline

    Measured: at end of treatment (an average of 4 years)

  14. Patient-reported outcomes according to PGIC

    Patient-reported outcomes according to Patient global impression of change (PGIC) form, evaluation of change in QoL from baseline

    Measured: at end of treatment (an average of 4 years)

  15. Patient-reported outcomes according to PGIS

    Patient-reported outcomes according to Patient global impression of severity (PGIS) form, evaluation of change in QoL from baseline

    Measured: at end of treatment (an average of 4 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2023
  2. Study start6 Dec 2023
  3. Primary completion1 Dec 2025
  4. Study completionNov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05782127
Sponsor's protocol ID
GFM-ONUVEN-MDS
Other IDs
2022-000634-41
Status last verified
Aug 2026
First submitted
23 Feb 2023
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Onureg + Venetoclax in people with Untreated Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 25 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (time frame: at day 28 of cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05782127.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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